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Background: Insulin resistance (IR) is related with adverse outcomes of in vitro fertilization (IVF) in women with obesity, but little is known about the relationship between IR and unexpected poor ovarian response (uPOR) in non-obese subjects with sufficient ovarian parameters (classified as POSEIDON group 1). This research aims to explore the association between the homeostasis model assessment of insulin resistance (HOMA-IR) and uPOR in non-obese women with normal biomarkers of ovarian reserve., Methods: The retrospective cohort study was conducted at a fertility center. The main inclusion criteria were age < 35 years, body mass index (BMI) < 28 kg/m 2 , normal ovarian reserve (anti-Mullerian hormone ≥ 1.2 ng/ml, antral follicle count ≥ 5). Women undergoing the first oocyte retrieval cycle were included consecutively between 2018 until 2023. Patients who have ≤ 9 oocytes retrieved were defined as uPOR. The multivariable logistic model and subgroup analysis were conducted after adjusting confounders., Results: A total of 6977 cycles were included. The adjusted odds ratio was 1.25 (95% confidence interval [CI], 1.12-1.39) for the increment of Ln HOMA-IR which was taken as a continuous variable. Meanwhile, as a sensitivity analysis, elevated tertile of HOMA-IR exhibited an increase in risk of uPOR for the third tertile (≥ 2.75) when compared with the first tertile (< 1.75) with OR of 1.33 (95%CI, 1.15-1.54). In the subgroup analysis, the positive association remained consistent., Conclusion: Elevated HOMA-IR values is significantly associated with increased risk of uPOR in non-obese women classified as POSEIDON group 1. Our study provided evidence for the adverse influence of IR on the ovarian response during IVF and shed light on the importance of IR measurement at the time of pre-stimulation among non-obese women., (© 2024. The Author(s).)

Background: Resveratrol is a natural polyphenolic compound present in plants and red wine with many potential health benefits. This compound has various anti-inflammatory and anti-tumor properties and can improve cellular mitochondrial activity. This trial was designed to evaluate the effect on the outcome of IVF of Resveratrol supplementation in women > 35 years with good ovarian reserve (AMH > 1.2 ng/ml). Women were randomized to receive or placebo or Resveratrol (150 mg per day) for three months preceding the ovarian stimulation (OS). All patients were stimulated with a starting dose of recombinant FSH ranging between 150 and 300 IU according to age and ovarian reserve. GnRH antagonist flexible protocol was adopted for pituitary suppression. Triggering was performed with urinary hCG (10.000 IU)., Results: The study was conducted between January 2019 and December 2022 with aa total of 37 cases and 33 controls were recruited. No statistically significant differences in the number of oocytes retrieved, biochemical pregnancy, clinical pregnancy and live birth rates were observed between women treated with resveratrol and control group. A statistically significant increase in the follicle output rate (FORT) and follicle-to oocyte index (FOI) was observed in women treated with resveratrol-based nutraceutical (0.92 versus 0.77 [p = 0.02], and 0.77 versus 0.64 [p = 0.006], respectively)., Conclusions: Preliminary results from this study indicate that pre-treatment with resveratrol may improve ovarian sensitivity to exogenous FSH, which in turn may decrease the risk of hypo-response to OS in advanced reproductive age women., (© 2024. The Author(s).)

Background and Objectives : The objective of this study was to evaluate the impact of adjuvant letrozole administration during ovarian stimulation using the gonadotropin-releasing hormone (GnRH) antagonist protocol on treatment outcomes in women categorized into POSEIDON groups 3 and 4. Materials and Methods : This retrospective cohort study analyzed data from patients classified into POSEIDON groups 3 and 4 who underwent fresh embryo transfer subsequent to intracytoplasmic sperm injection following a GnRH antagonist stimulation protocol between January 2017 and December 2021. Patients were divided into two groups: the GnRH-LZ group, who received letrozole at a dosage of 5 mg/day for five consecutive days, and the GnRH-ant group, who did not receive adjuvant letrozole. The primary outcome measure of the study was a comparative analysis of live birth rates between the two groups. Results : A total of 449 patients were deemed suitable for final analysis and were allocated into two groups: 281 patients in the GnRH-ant group and 168 patients in the GnRH-LZ group. Live birth rates were found to be comparable in both groups (11% vs. 9%, p = 0.497). Letrozole administration significantly reduced the total amount of gonadotropins required (2606.2 ± 1284.5 vs. 3097.8 ± 1073.3, p < 0.001), the duration of ovarian stimulation (11.2 ± 3.9 vs. 10.2 ± 3, p = 0.005), and the serum peak estradiol concentration (901.4 ± 599.6 vs. 463.8 ± 312.3, p < 0.001). Conclusions : Adjuvant letrozole administration did not demonstrate a significant impact on live birth rates among women categorized into POSEIDON groups 3 and 4. However, this approach may offer potential cost reductions by diminishing the necessity for exogenous gonadotropins and shortening the duration of ovarian stimulation.

Purpose: To evaluate the effects of adjuvant letrozole administration on outcomes of gonadotropin-releasing hormone (GnRH) antagonist cycles with intra-cytoplasmic sperm injection in POSEIDON groups 3 and 4 expected poor responder women., Methods: This study was conducted by retrospective analysis of patients with expected poor ovarian response (POSEIDON groups 3 and 4) that underwent GnRH antagonist cycles with intra-cytoplasmic sperm injection between 2010 and 2020. A total of 488 patients with letrozole co-administration and 2564 patients without any adjuvant treatment that underwent GnRH antagonist cycles within the selected period of time were included in the study., Results: Implantation rates, clinical pregnancy rates and live birth delivery rates were significantly higher in letrozole administered patients in comparison to controls among POSEIDON group 3 women (0.39 ± 0.46 vs 0.27 ± 0.40, p = 0.01; 46.1% vs 33%, p = 0.014; 42.7% vs 31.5%, p = 0.034, respectively). Mean total doses of gonadotropins required per cycle were significantly lower in letrozole administered patients among both POSEIDON groups 3 and 4 women (2864.65 ± 878.47 IU vs 3757.27 ± 1088.89 IU, p < 0.001; 3286.06 ± 770.16 IU vs 3666.48 ± 959.66 IU, p < 0.001, respectively)., Conclusion: Adjuvant letrozole co-administration in intra-cytoplasmic sperm injection cycles following GnRH antagonist protocol appears to improve implantation, clinical pregnancy and live birth delivery rates in women with POSEIDON group 3 expected poor ovarian response., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mild stimulation (MS) consists in prescribing gonadotropin at the minimum amount alone or in combination with other compounds. This strategy has gained popularity in assisted reproduction for the reduced costs, better patient compliance, and reduced risk of hyperstimulation syndrome. Some investigators proposed MS even in women with low prognosis. The Poseidon group proposed new criteria to identify these patients categorizing them into 4 different groups, each one characterized by a specific segment of prognosis. The use of MS in women with low prognosis involves risks that cannot be overlooked. The most crucial concerns are the increased rate of cycle cancellation and the reduced number of eggs collected. Notably, the number of eggs collected still represents the most accurate predictor of live birth and cumulative live birth rate. Despite promising preliminary data, recent evidence has confirmed that MS does not improve gamete quality. Hence, considering that no robust strategy was identified so far to improve oocyte quality, the only reasonable strategy to improve the chance of live birth in women with low prognosis is to collect the necessary number of oocytes to maximize the probability to obtain at least 1 good-quality embryo. In this sense, conventional protocols offer better results when compared with the mild approach. Given the difficulty in collecting enough oocytes in a single round of stimulation, accumulation strategy could represent a valuable approach especially in women with advanced reproductive age and reduced ovarian reserve., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Poor ovarian response remains one of the most challenging tasks for an IVF clinician. In this review, we aim to highlight the ongoing research for optimizing the prognosis in poor ovarian response patients. The newly introduced POSEIDON criteria argue that the first step is to move from a poor response to a poor prognosis concept, while improving identification and stratification of the different sub-types of poor prognosis patients prior to ovarian stimulation. The immediate marker of success is the ability of the ovarian stimulation to retrieve the number of oocytes needed to obtain at least one euploid blastocyst for transfer in each patient. This surrogate marker of success should not replace live birth as the most important outcome, but it should be approached as a useful tool for clinicians to evaluate their strategy for achieving live birth in the shortest timespan possible in the individual patient/ couple.

Objective: The objective of this study was to examine whether the combined Stop GnRH-agonist (GnRH-ag), letrozole priming, and multiple-dose GnRH-antagonist (GnRH-ant) protocol may improve in vitro fertilization/intracytoplasmic sperm injection cycle in poor ovarian responders (PORs)., Design: This was a historical cohort, proof of concept study under tertiary setting at University affiliated Medical Center., Patients: Five PORs fulfilling the POSEIDON Group 4 criteria were included., Main Outcome Measures: Number of oocytes retrieved, number of top-quality embryos (TQEs), and controlled ovarian hyperstimulation (COH) variables were the main outcome measures., Results: The combined Stop GnRH-ag, letrozole priming, and multiple-dose GnRH-ant COH protocol revealed significantly higher number of follicles >13 mm on the day of hCG administration and higher number of oocytes retrieved, with non-significantly more TQEs and a reasonable clinical pregnancy rate., Conclusions: The combined Stop GnRH-ag, letrozole priming, and multiple-dose GnRH-ant COH protocol is a valuable tool in the armamentarium for treating POSEIDON Group 4 patients. Further large prospective studies are needed to elucidate its role in POR and to identify the specific characteristics of women (before initiating ovarian stimulation) that will aid both fertility specialists' counseling and their patients in adjusting the appropriate COH protocol., (© 2021 S. Karger AG, Basel.)

Objectives: The aim of the study was to assess the prevalence of "low prognosis" patients using POSEIDON criteria undergoing in vitro fertilization (IVF) cycle in Indian population. Study Design: This is a retrospective cohort study. Period of Study: It included data from the recruitment period from January 1, 2018 to December 31, 2021. Study Settings: The study was conducted at the Center for IVF and Human Reproduction, Sir Gangaram Hospital, New Delhi. Methodology: Out of the 3032 IVF stimulation cycles with oocyte aspirations, 596 cycles were excluded based on the exclusion criteria. The study focused on 2436 IVF/ICSI (Intracytoplasmic sperm injection) stimulation cycles that met inclusion criteria. Each cycle was categorized into one of the four groups defined by the POSEIDON criteria along with a fifth non-POSEIDON group. Prevalence was observed for each POSEIDON group and the non-POSEIDON group. Results: Out of the analyzed cycles, 1210 were classified under POSEIDON groups, representing a prevalence of 49.67%. The distribution of cycles in POSEIDON groups 1, 2, 3, and 4 was 31.4, 23.2, 19.17, and 26.19%, respectively. Conclusion: Low prognosis patients based on POSEIDON criteria, represented about half of the population. [ABSTRACT FROM AUTHOR]

Background: Poor responders may benefit from recruiting a 'second wave' of antral follicles within the same cycle. This concept forms the basis of double stimulation which has been named as 'DuoStim'. This protocol involves ovarian stimulation in both follicular and luteal phases with egg retrieval in each phase, respectively, to increase the number of oocytes and embryos in one menstrual cycle. This can be considered a potentially valuable option for women with poor ovarian reserve/response to maximise the number of oocytes retrieved in a single ovarian cycle in the shortest possible time. Aims: The aim of this study was to evaluate the efficacy of the DuoStim protocol in women classified as POSEIDON poor responders undergoing in vitro fertilization by comparing the embryological outcomes between the follicular and luteal phase stimulations in the same menstrual cycle. Settings and Design: This was a retrospective cohort study of 131 patients who enrolled to undergo DuoStim cycles from January 2021 to Sept. 2022, at a IVF center in a tertiary care hospital. Materials and Methods: The follicular phase stimulation used a standard antagonist protocol for the first oocyte retrieval. Thereafter, the luteal phase stimulation was started 3 days after the first retrieval, with the same dose of gonadotropin along with a daily 10 mg medroxyprogesterone acetate tablet, followed by a second oocyte retrieval. Blastocysts produced in both the phases were subsequently vitrified. Statistical Analysis Used: The paired t-test was used for comparing means and 95% confidence intervals (CIs) for different parameters. McNemar's test was used to compare paired proportions. The analysis was conducted using R statistical environment 4.2. Results: The mean number of oocytes retrieved and the mean number of utilizable blastocysts frozen per stimulation cycle were found to be significantly higher in the luteal phase as compared to the follicular phase (5.71 ± 3.95 vs. 4.87 ± 2.79, P = 0.02, and 1.43 ± 1.22 vs. 0.95 ± 1, P = 0.001, respectively). However, the mean fertilization rate and the mean blastocyst utilization rate were found to be similar between both the phases. The length of stimulation was found to be approximately 3 days longer in the luteal phase (12.63 ± 2.43 vs. 9.75 ± 1.85, P = 0.001). Overall, the odds of obtaining a usable blastocyst in the luteal phase was found to be significantly higher than in the paired follicular phase (73.9% vs. 57.7%, P = 0.012, odds ratio: 2.286 [95% CI: 1.186-4.636]). Also importantly, the luteal phase stimulation was able to rescue 68% (32/47) of patients where no blastocysts were formed in the follicular phase. Conclusion: Our data demonstrate that in women with poor reserve, the addition of luteal stimulation could increase the chances of achieving a pregnancy by significantly increasing the number of eggs and transferable embryos per menstrual cycle compared to follicular stimulation alone. Furthermore, luteal phase stimulation in the same cycle proved to be an effective strategy to rescue POSEIDON poor responders with no embryos after the first stimulation. [ABSTRACT FROM AUTHOR]

Aim of this study was to evaluate the effects of dual triggering with gonadotropin releasing hormone agonist and human chorionic gonadotropin (hCG) on outcomes of fresh embryo transfers following gonadotropin antagonist cycles in POSEIDON group 3 and group 4 low prognosis women and to compare the outcomes with hCG-only triggering. This study was conducted by retrospective analysis of patients with expected poor ovarian response (POSEIDON group 3 and 4) that underwent fresh embryo transfers following in-vitro fertilization/intracytoplasmic sperm injection cycles with either dual triggering or hCG-only triggering between January 2010 and April 2020. A total of 1068 women that underwent dual triggering and 1931 that underwent hCG-only triggering were included in the study. Number of retrieved oocytes, M2 oocytes, oocyte maturation rate, fertilization rate, obtained 2PN embryos, implantation rate, clinical pregnancy rate and live birth delivery rates were found significantly higher in dual-triggering group in comparison to hCG-only group (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.02, p < 0.001 respectively). Dual trigger with concomitant injections of GnRH agonist and hCG in GnRH antagonist cycles appears to improve IVF outcomes, increase quality of embryos, reduce miscarriage rates and consequently increase live birth delivery rates in POSEIDON groups 3/4 poor responders. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether minimal ovarian stimulation (mOS) is as effective as conventional ovarian stimulation (cOS) for older women belonging to different groups according to the Poseidon criteria. Material and methods: Observational retrospective multicentre cohort including women from Poseidon's groups 2 and 4 that underwent in vitro fertilization (IVF). We performed a mixed-effects logistic regression model, adding as a random effect the patients and the stimulation cycle considering the dependence of data. Survival curves were employed as a measure of the cumulative live birth rate (CLBR). The primary outcomes were live birth rate per embryo transfer and CLBR per consecutive embryo transfer and oocyte consumed until a live birth was achieved. Results: A total of 2002 patients underwent 3056 embryo transfers (mOS = 497 and cOS = 2559). The live birth rates per embryo transfer in mOS and cOS showed no significant difference in both Poseidon's groups. Likewise, the logistic regression showed similar live birth rates between the two protocols in Poseidon's groups 2 (OR 1.165, 95% CI 0.77–1.77; p = 0.710) and 4 (OR 1.264 95% CI 0.59–2.70; p = 0.387). However, the survival curves showed higher CLBR per oocyte in women that received mOS (Poseidon group 2: p < 0.001 and Poseidon group 4: p = 0.039). Conclusions: Minimal ovarian stimulation is a good alternative to COS as a first-line treatment for patients belonging to Poseidon's groups 2 and 4. The number of oocytes needed to achieve a live birth seems inferior in mOS strategy than cOS. [ABSTRACT FROM AUTHOR]

Background: Poor ovarian reserve and a high rate of pregnancy failure associated with low quality and quantity of oocytes are observed in poor responders to in vitro fertilization. Objective: To assess the effect of age, body mass index (BMI), endometriosis, and history of ovarian surgery on ovarian reserve in a group of poor responders. Materials and Methods: In this cross-sectional study 749 women who referred to Yasmin Clinic of Dr. Cipto Mangunkusumo National General Hospital from January 2013 to June 2017 were enrolled. Two definitions of poor responders and Poseidon criteria and consecutive sampling techniques were used. Participants were divided into good and poor responder groups based on the ovarian reserve test; participant with oocyte ≤ 3 was classified as a poor responder. Based on this, 188 participants with nine (4-47) oocytes were included in the poor responder group. While, good responder comprised of two (0-3) oocytes. Results: Age and anti-Mullerian hormone level (AMH) were significantly associated with ovarian reserve in the poor-responder group (p < 0.001). However, in multivariate analyses, age was the only significant predictor of ovarian response in the poorresponder group (p = 0.004). While endometriosis was the significant predictor of Poseidon groups 1 and 4, surgical history was the significant predictor of Poseidon groups 2 and 3. Meanwhile, an increase in BMI decreased the risk of classification under Poseidon group 3. Conclusion: Age, AMH, BMI, endometriosis, and history of ovarian surgery affected the risk of classification of the Poseidon group. [ABSTRACT FROM AUTHOR]

Objective: To investigate ovarian sensitivity in subgroups of patients with a low prognosis, as defined by the POSEIDON criteria, undergoing in vitro fertilization treatment and measures to improve ovarian sensitivity in these patients. Design: We conducted a retrospective cohort analysis. Setting: The study was conducted at an IVF clinic in a public hospital. Patients: A total of 32,128 fresh IVF cycles from January 2014 to October 2018 at a single IVF clinic were included in the analysis. Patients with a low prognosis were categorized into four groups based on the POSEIDON criteria. Interventions: None. Main Outcome Measure: The primary outcome measures were the follicular output rate (FORT) and the follicle-to-oocyte index (FOI). Results: The FORTs in the order from the highest to the lowest were 1.18 in group 3, 0.98 in group 4, 0.76 in group 1, and 0.68 in group 2. The trend in the FOI values was consistent with that in the FORTs. Among patients with poor ovarian sensitivity, 58.41% of patients with FORTs ≥ 0.30 in the second cycle underwent an adjustment to the ovarian stimulation (OS) protocol and 41.59% underwent an adjustment to the gonadotropin (Gn) starting dose. Among patients with normal ovarian sensitivity, 43.56% of those with FORTs ≥ 0.80 in the second cycle underwent an adjustment to the OS protocol and 56.44% underwent an adjustment to the Gn starting dose. Conclusion: Ovarian sensitivity was the highest in group 3 (young women with poor ovarian reserve), followed by groups 4 (women at advanced age with poor ovarian reserve) and 1 (young women with good ovarian reserve), and it was the lowest in group 2 (women at advanced age with good ovarian reserve). For patients with poor ovarian sensitivity, it is preferred to recommend an adjustment to the OS protocol, while for those with normal ovarian sensitivity, adjusting the Gn starting dose is preferred. [ABSTRACT FROM AUTHOR]